The ability of bacterial pathogens to invade host cells can have profound effects on the establishment, persistence, and propagation of infections. By entering host cells and subsequently avoiding destruction within degradative lysosomes, bacteria can gain better access to scarce resources as well as protection from host defenses and antibiotics. Furthermore, host cell invasion can facilitate the dissemination of bacteria within and across tissue barriers. The actual benefits afforded to intracellular bacterial pathogens can be highly context-dependent and sometimes difficult to discern. Over the past three decades, a number of bacterial species that were conventionally thought to be strictly extracellular pathogens were found to have alternative intracellular lifestyles (1, 2). Among these facultative intracellular pathogens are strains of uropathogenic Escherichia coli (UPEC) and other bacteria that cause urinary tract infections (UTIs). These infections are very common, especially among females, and are prone to recur even after treatment with appropriate antibiotics (3, 4). Nearly one-third of women will have an acute UTI by the age of 24, and about 25% of these individuals will experience at least one recurrent UTI within 6 months of the initial infection. Many individuals endure painful bouts of recurrent and chronic UTIs throughout their lives (5). The capacity of some uropathogens to persist and even multiply within host cells may help explain why some UTIs repeatedly recur while also opening the door for new treatment options.

Localization of UPEC within the bladder urothelium. (A, B) Confocal images of tissue sections from infected mouse bladders show IBCs (green) within umbrella cells (UC). F-actin (red) is sparse within these host cells but dense within the underlying immature cells (IC). A single bacterium, localized within a LAMP-1-positive compartment (blue) and surrounded by F-actin, is visible within one of the immature cells (box). (C–E) Images show magnified views of the area that is boxed in (B). Figures are reprinted from Cellular Microbiology (26) with permission of the publisher.

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Figure 2

Localization of UPEC within the bladder urothelium. (A, B) Confocal images of tissue sections from infected mouse bladders show IBCs (green) within umbrella cells (UC). F-actin (red) is sparse within these host cells but dense within the underlying immature cells (IC). A single bacterium, localized within a LAMP-1-positive compartment (blue) and surrounded by F-actin, is visible within one of the immature cells (box). (C–E) Images show magnified views of the area that is boxed in (B). Figures are reprinted from Cellular Microbiology (26) with permission of the publisher.

The efflux and filamentation of UPEC coincident with the exfoliation of IBC-containing umbrella cells. (A–C) Scanning electron microscopy images show filamentous forms of UPEC, as well as their normal-sized counterparts, emerging from within IBCs. (D) Image from a hematoxylin- and eosin-stained bladder section highlights the ability of filamentous UPEC forms to extend long distances through umbrella cells. (E) Confocal image shows an IBC (blue) in close association with cytokeratin intermediate filaments (green) within an umbrella cell that is undergoing exfoliation. LAMP-1-positive compartments are red. Scale bars = 5 μm (A–C); 10 μm (D, E). Images are from mouse bladders recovered 6 hours after transurethral inoculation with UPEC. The figures are modified from Cellular Microbiology (26) or reprinted from Infection and Immunity (17) with permission of the publishers.

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Figure 3

The efflux and filamentation of UPEC coincident with the exfoliation of IBC-containing umbrella cells. (A–C) Scanning electron microscopy images show filamentous forms of UPEC, as well as their normal-sized counterparts, emerging from within IBCs. (D) Image from a hematoxylin- and eosin-stained bladder section highlights the ability of filamentous UPEC forms to extend long distances through umbrella cells. (E) Confocal image shows an IBC (blue) in close association with cytokeratin intermediate filaments (green) within an umbrella cell that is undergoing exfoliation. LAMP-1-positive compartments are red. Scale bars = 5 μm (A–C); 10 μm (D, E). Images are from mouse bladders recovered 6 hours after transurethral inoculation with UPEC. The figures are modified from Cellular Microbiology (26) or reprinted from Infection and Immunity (17) with permission of the publishers.

UPEC invasion of bladder epithelial cells. (A) Model depicts host and bacterial factors that have been identified as regulators of bladder cell invasion by UPEC. Potential therapeutics are also indicated. (B) The host factors that can modulate the FimH-dependent entry of UPEC into bladder cells are interconnected. The image in (B) was created using the STRING database (version 10.0) of known and predicted protein-protein interactions (198). Line thickness indicates the strength of the supporting data.

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Figure 4

UPEC invasion of bladder epithelial cells. (A) Model depicts host and bacterial factors that have been identified as regulators of bladder cell invasion by UPEC. Potential therapeutics are also indicated. (B) The host factors that can modulate the FimH-dependent entry of UPEC into bladder cells are interconnected. The image in (B) was created using the STRING database (version 10.0) of known and predicted protein-protein interactions (198). Line thickness indicates the strength of the supporting data.